Funtion and differentiation of a specialized subset of intestinal epithelial M cells

• Project/Area Number: 21390155
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: OHNO Hiroshi 独立行政法人理化学研究所, 免疫系構築研究チーム, チームリーダー (50233226)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2011: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2010: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2009: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: 腸管免疫系 / M細胞 / 抗原取り込み / RANKL / Spi-B / 遺伝子欠損マウス / 腸管免疫応答 / マイクロアレイ / 腸管免疫 / miRNA / Dicer / GPIアンカータンパク質 / Citrobacter rodentium / LTa / b / RANK

Research Abstract

Taking advantage of the fact that exogenously administered RANKL induces ectopic M-cell differentiation in murine small intestinal epithelium, we established an evaluation system for M-cell differentiation. By using the system, we have identified the transcription factor Spi-B to be specifically expressed in M cells and essential for their differentiation. Spi-B KO mice, lacking M cells, failed to evoke normal immune responses toward orally infected Salmonella Typhimurium, indicating that antigen uptake by M cells is critical for efficient intestinal immune responses.

Research Products

• [Journal Article] Bifidobacteria can protect from enteropathogenic infection through production of acetate (2011)
  • Author(s): Fukuda, S., Toh, H., Hase, K., Oshima, K., Nakanishi, Y., Yoshimura, K., Tobe, T., Clarke, J. M., Topping, D. L., Suzuki, T., Taylor, T. D., Itoh, K., Kikuchi, J., Morita, H., Hattori, M., Ohno, H.
  • Journal Title: Nature Volume: 469 Pages: 543-547
  • Peer Reviewed
• [Journal Article] CCR6hiCD11cint B cells promote M-cell differentiation in Peyer's patch (2011)
  • Author(s): Ebisawa, M., Hase, K., Takahashi, D., Kitamura, H., Knoop, K. A., Williams, I. R., Ohno, H.
  • Journal Title: Int. Immunol Volume: 23 Pages: 261-269
  • Peer Reviewed
• [Journal Article] Application of a mouse ligated Peyer's patch intestinal loop assay to evaluate bacterial uptake by M cells (2011)
  • Author(s): Fukuda S, Hase K, Ohno H.
  • Journal Title: J Vis Exp Volume: 17 Pages: 3225-3225
  • Peer Reviewed
• [Journal Article] CCR6hiCD11cint B cells promote M-cell differentiation in Peyer's patch (2011)
  • Author(s): Ebisawa, M., et al
  • Journal Title: Int.Immunol. Volume: 23 Issue: 4 Pages: 261-269
  • DOI: 10.1093/intimm/dxq478
  • Peer Reviewed
• [Journal Article] M cell-depletion blocks oral prion disease pathogenesis (2011)
  • Author(s): Donaldson, D.S., et al
  • Journal Title: Mucosal Immunol Volume: 5 Issue: 2 Pages: 216-225
  • DOI: 10.1038/mi.2011.68
  • Peer Reviewed
• [Journal Article] Dynamic Omics Approach Identifies Nutrition-Mediated Microbial Interactions (2011)
  • Author(s): Nakanishi, Y., et al.
  • Journal Title: J.Proteome Res. Volume: 10 Pages: 824-836
  • Peer Reviewed
• [Journal Article] Bifidobacteria can protect from enteropathogenic infection through production of acetate (2011)
  • Author(s): Fukuda, S., et al.
  • Journal Title: Nature Volume: 4692 Pages: 543-547
  • Peer Reviewed
• [Journal Article] Identification of TOSO/FAIM3 as an Fc receptor for IgM (2011)
  • Author(s): Shima H., et al.
  • Journal Title: Int.Immunol. Volume: 22 Pages: 149-156
  • Peer Reviewed
• [Journal Article] Identification of TOSO/FAIM3 as an Fc receptor for IgM (2010)
  • Author(s): Shima, H., Takatsu, H., Fukuda, S., Ohmae, M., Hase, K., Kubagawa, H., Wang, J.-Y., Ohno, H.
  • Journal Title: Int. Immunol Volume: 22 Pages: 149-156
  • NAID: 10027391592
  • Peer Reviewed
• [Journal Article] Uptake through Glycoprotein 2 of FimH^+bacteria by M cells initiates mucosal immune response (2009)
  • Author(s): Hase, K., Kawano, K., Nochi, T., Pontes, G. S., Fukuda, S., Ebisawa, M., Kadokura, K., Tobe, T., Fujimura, Y., Kawano, S., Nakato, G., Kimura, S., Murakami, T., Iimura, M., Hamura, K., Fukuoka, S. I., Lowe, A. W., Waguri, S., Itoh, K, Kiyono, H., Ohno, H.
  • Journal Title: Nature Volume: 462 Pages: 226-230
  • Peer Reviewed
• [Journal Article] M-Sec promotes membrane nanotube formation by interacting with Ral and the exocyst complex (2009)
  • Author(s): Hase, K., Kimura, S., Takatsu, H., Ohmae, M., Kawano, S., Kitamura, H., Ito, M., Watarai, H., Hazelet, C. C., Yeaman, C., Ohno, H.
  • Journal Title: Nature Cell Biol Volume: 11 Pages: 1427-1432
  • Peer Reviewed
• [Journal Article] New approach for M-cell-specific molecules screening by comprehensive transcriptome analysis (2009)
  • Author(s): Nakato, G., Fukuda, S., Hase, K., Goitsuka, R., Cooper, M. D., Ohno, H.
  • Journal Title: DNA Res Volume: 16(4) Pages: 227-235
  • Peer Reviewed
• [Journal Article] Uptake via Glycoprotein 2 of FimH+ bacteria by M cells initiates mucosal immune response (2009)
  • Author(s): Hase, K., et al.
  • Journal Title: Nature 462 Pages: 226-230
  • Peer Reviewed
• [Journal Article] M-Sec promotes membrane nanotube formation by interacting with Ral and the exocyst complex (2009)
  • Author(s): Hase, K., et al.
  • Journal Title: Nat.Cell Biol. 11 Pages: 1427-1432
  • Peer Reviewed
• [Journal Article] New approach for M-cell-specific molecules screening by comprehensive transcriptome analysis (2009)
  • Author(s): Nakato, G., et al.
  • Journal Title: DNA Res. 16 Pages: 227-235
  • Peer Reviewed
• [Journal Article] The Ets transcription factor Spi-B is essential for the differentiation of intestinal M cells
  • Author(s): Kanaya, T., Hase, K., Takahashi, D., Fukuda, S., Hoshino, K., Sasaki, I., Hemmi, H., Knoop, K. A., Kumar, N., Sato, M., Katsuno, T., Yokosuka, O., Toyooka, K., Nakai, K., Sakamoto, A., Kitahara, Y., Jinnohara, T., McSorley, S. J., Kaisho, T., Williams, I.
  • Journal Title: Nat. Immunol. Volume: (in press)
  • Peer Reviewed
• [Presentation] Role of Commensal Microbiota in Intestinal Immunity and Host Defense (2012)
  • Author(s): Ohno, H.
  • Organizer: The 3rd International Forum, The 98th General Meeting of the Japanese Society of Gastroenterology
  • Place of Presentation: 東京
  • Year and Date: 2012-04-20
• [Presentation] M細胞に発現するプリオンタンパク質はBrucella abortusの取り込み受容体として機能する (2011)
  • Author(s): 中藤学、長谷耕二、鈴木道夫、西田教行、堀内基広、阿戸学ぶ、大野博司
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-29
• [Presentation] NALTにおけるM細胞を介した粘膜免疫応答 (2011)
  • Author(s): 伊達康博、海老澤昌史、福田真嗣、尾畑祐樹、高橋大輔、嶋秀明、花里美紗穂、中藤学、常田聡、Williams, I. R.、長谷耕二、大野博司
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-28
• [Presentation] 腸管関連リンパ組織形成における上皮性Notchシグナルの役割。 (2011)
  • Author(s): 尾畑祐樹、海老澤昌史、杉山真知子、長谷耕二、大野博司
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-28
• [Presentation] The Fc receptor for IgM(Fc R) plays an important role in humoral immune responses to low-dose antigen (2011)
  • Author(s): Ouchida, R., Mori, H., Hase, K., Kurosaki, T., Tokuhisa, T., Ohno, H., Wang, J.-Y
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-28
• [Presentation] Function and differentiation of M cells, a unique subset of intestinal epithelial cells important for mucosal immunity (2011)
  • Author(s): Ohno, H.
  • Organizer: Plenary Lecture
  • Place of Presentation: Cairns, Australia
  • Year and Date: 2011-09-28
• [Presentation] Function and differentiation of M cells, a unique subset of intestinal epithelial cells important for mucosal immunity (2011)
  • Author(s): Ohno, H
  • Organizer: ComBio2011
  • Place of Presentation: Cains, australia(招待講演)
  • Year and Date: 2011-09-28
• [Presentation] The role of M-Sec in tunneling nanotube formation (2011)
  • Author(s): Ohno, H
  • Organizer: EMBO Meeting 2011
  • Place of Presentation: Vienna, Austria(招待講演)
  • Year and Date: 2011-09-11
• [Presentation] The role of M-Sec in tunneling nanotube formation. EMBO Meeting (2011)
  • Author(s): Ohno, H., Hase, K., Kimura, S., Fukai, S.
  • Organizer: 2011 Workshop 'Role of nanotubes in intercellular signaling'
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2011-09-10
• [Presentation] 食物アレルギーと腸管免疫・経口免疫寛容。 (2011)
  • Author(s): 大野博司
  • Organizer: 第18回日本免疫毒性学会シンポジウム
  • Place of Presentation: 千葉
  • Year and Date: 2011-09-08
• [Presentation] M Cells and Antigen Delivery to DCs in the Gut (2011)
  • Author(s): Hase, K., Kawano, K., Ebisawa, M., Ohno, H.
  • Organizer: Keystone Symposia 'Dendritic Cells and the Initiation of Adaptive Immunity(J7)'
  • Place of Presentation: Santa Fe, NM, USA
  • Year and Date: 2011-02-16
• [Presentation] M cells and Antigen Delivery to DCs in the Gut (2011)
  • Author(s): Ohno H.
  • Organizer: Keystone Syposia
  • Place of Presentation: Santa Fe, NM, USA
  • Year and Date: 2011-02-16
• [Presentation] M-Sec : a promoter of tunneling nanotube formation (2010)
  • Author(s): Ohno, H.
  • Organizer: Biochemistry and Molecular Biology 2010
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-12-09
• [Presentation] 食物アレルギーと腸管免疫・経口免疫寛容 (2010)
  • Author(s): 大野博司
  • Organizer: 第60回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
  • Year and Date: 2010-11-27
• [Presentation] GP2-dependent antigen transcytosis by M cells intiates antigen-specific mucosal immune response (2010)
  • Author(s): Hase, K., Nochi, T., Pontes, G. S., Fukuda, S., Ebisawa, M., Kadokura, K., Kiyono, H., Ohno, H.
  • Organizer: 14th International Congress of Immunology(ICI 2010)
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-26
• [Presentation] Identification of TOSO/FAIM3 as an Fc receptor for IgM (2010)
  • Author(s): Shima, H., Takatsu, H., Fukuda, S., Ohmae, M., Hase, K., Kubagawa, H., Wang, J.-Y., Ohno, H.
  • Organizer: 14th International Congress of Immunology(ICI 2010)
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-25
• [Presentation] Glycoprotein 2 : An Antigen-Uptake Receptor on Intestinal Epithelial M Cells for Mucosal Immunity (2010)
  • Author(s): Ohno, H.
  • Organizer: Traffc Symposium
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-06-04
• [Presentation] Bacterial recognition and uptake by M cells (2010)
  • Author(s): Ohno, H.
  • Organizer: The 63rd Annual Meeting of the Japan Society for Cell Biology
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2010-05-21
• [Presentation] Distinct miRNA expression Profiles of Follicle-associated Epithelium(FAE) and Villous Epithelium(VE) (2010)
  • Author(s): Nakato, G., Hase, K., Ohno, H.
  • Organizer: 19th CDB Meeting : RNA Sciences in Cell and Developmental Biology
  • Place of Presentation: 神戸
  • Year and Date: 2010-05-12
• [Presentation] Identification of RNA aptamers targeting mouse GP2 proteins by SELEX (2009)
  • Author(s): Hanazato, M., Nakato, G., Nishikawa, F., Hase, K. Nishikawa, S., Ohno, H.
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-11
• [Presentation] CCR6^<hi> CD11c^+B cells promote M-cell differentiation in Peyer's patch (2009)
  • Author(s): Ebisawa, M., Hase, K., Takahashi, D., Kitamura, H., Williams, I. R., Ohno, H.
  • Organizer: 第32回日本分子生物学会年会ワークショップ
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] Multiple Omics Identified Microbial Metabolites to Protect Host from Enterohemorrhagi Escherichia coli O157:H7 Lethal Infection (2009)
  • Author(s): Fukuda, S.
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] CCR6^<hi> CD11c^+ B cells promote M-cell differentiation in Peyer's patch (2009)
  • Author(s): Ebisawa, M.
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] Identification of microRNAs in LPS-stimulated macrophage-like cells (2009)
  • Author(s): Shimura, N.
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] GP2-dependent antigen transcytosis by M cells initiates antigen-specific mucosal immune response (2009)
  • Author(s): 長谷耕二
  • Organizer: 第39回日本免疫学会総会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-04
• [Presentation] GP2-dependent antigen transcytosis by M cells initiates antigen-specific mucosal immune response (2009)
  • Author(s): Hase, K., Nochi, T., Pontes, G. S., Fukuda, S., Ebisawa, M., Kadokura, K., Kiyono, H., Ohno, H.
  • Organizer: 第39回日本免疫学会総会学術集会シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-02
• [Presentation] Functional analysis of CCL9 in the intestinal immune system (2009)
  • Author(s): Yamazaki, R., Kimura, S., Ebisawa, M., Date, Y., Tsuneda, S., Suzuki, H., Hase, K., Ohno, H.
  • Organizer: 第39回日本免疫学会総会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-02
• [Presentation] Spatial and temporal specific expression patterns of RANK and RANKL in developing peripheral lymphoid organs (2009)
  • Author(s): Sugiyama. M.
  • Organizer: 第39回日本免疫学会総会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-02
• [Presentation] M-Secによる細胞間ナノチューブ形成促進の分子機構 (2009)
  • Author(s): 長谷耕二、高津宏之、木村俊介、大野博司
  • Organizer: 第61回日本細胞生物学会大会ワークショップ
  • Place of Presentation: 名古屋
  • Year and Date: 2009-06-03
• [Presentation] M-Secによる細胞間ナノチューブ形成促進の分子機構 (2009)
  • Author(s): 長谷耕二
  • Organizer: 第61回日本細胞生物学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-06-03
• [Presentation] Functional analysis of CCL9 in the intestinal immune system (2009)
  • Author(s): Yamazaki, R., Kimura, S., Hase, K., Ebisawa, M., Date, Y., Tsuneda, S., Suzuki, H., Ohno, H.
  • Organizer: 第61回日本細胞生物学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-06-02
• [Presentation] Study on the process of antigen transcytosis by M cells (2009)
  • Author(s): Kimura, S., Sakamoto, A., Yamazaki, R., Kawano, K., Hase, K., Ohno, H.
  • Organizer: 第61回日本細胞生物学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-06-02
• [Book] 臨床粘膜免疫学 (2010)
  • Author(s): 大野博司
  • Publisher: シナジー
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